tbuckley/cabot-search huggingface dataset:
Abstract 11869: Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the Multi-Ethnic Study of Atherosclerosis
Authors: Mahsima Shabani, Min Wang, Gregory D Jenkins, Jerome I Rotter, Stephen S Rich, Anthony Batzler, Kent D Taylor, Josyf C Mychaleckyj, Duan Liu, Joao A Ac Lima, Naveen L Pereira
Journal: Circulation (2022)

Introduction: Genome-wide association studies have identified common genetic variants associated with hypertrophic (HCM) and dilated cardiomyopathy (DCM) and left ventricular (LV) characteristics. However, the association of these variants with myocardial fibrosis (MF), an important pathophysiological mediator of cardiomyopathy, is unknown. Hypothesis: We used the Multi-Ethnic Study of Atherosclerosis (MESA), to evaluate the association of these loci with interstitial MF measured by cardiac MRI (CMR). Methods: Unrelated MESA participants with T1-mapping CMR and no history of MI or heart failure were included (n=1,235). We used the extracellular volume (ECV) fraction as a well-established surrogate of interstitial MF. Genotyping was performed by Affymetrix Human SNP array 6.0, and imputation was performed using the TOPMED reference panel. Log ECV(%) was regressed on 50 candidate SNPs, in each ethnicity/race group, adjusting for age, sex, and population stratification principal component. The race-specific results were pooled by fixed-effect meta-analyses using METASOFT. Results: The SMARCB1 rs2186370 intronic variant, previously identified as a risk variant for DCM and HCM, was associated with ECV (p=0.0004). The rs2186370 A allele (frequency: 0.18 in Whites, and 0.50 in African Americans) was associated with a 1.6% increase in ECV. The rs2070458 A allele (another SMARCB1 intronic variant), in complete linkage disequilibrium with rs2186370, was known previously to be associated with increased LV wall thickness, mass, and concentricity. The direction of effect was similar in all four ancestry groups, but the effect was strongest in African Americans. These variants are strong expression quantitative loci (eQTLs) in human LV tissue and are associated with genotype-dependent expression of SMARCB1 ( p =7.3х10 -22 ) and MMP11 ( p =2.5х10 -24 ). Conclusions: In conclusion, variants in two linked SMARCB1 loci previously associated with HCM, DCM and LV traits, are associated with CMR-based interstitial MF. These loci are eQTL not only for SMARCB1 but also for MMP11 an important mediator of MF . These findings underscore the important link between MF and CM, and potentially provide novel mechanistic targets in understanding the development of CM.
Abstract 12680: Alcohol Consumption and Arrhythmia Recurrence After Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis
Authors: Alexander W Grindal, Robert Sparrow, William F McIntyre, David Conen, Jeff S Healey, Jorge Wong
Journal: Circulation (2022)

Introduction: Whether alcohol consumption increases the risk of atrial fibrillation (AF) recurrence following catheter ablation for AF remains unclear. We aimed to systematically review the medical literature to assess the impact of alcohol consumption on the recurrence of AF following AF Hypothesis: Elevated levels of alcohol consumption are associated with increased rates of AF recurrence following AF ablation. Methods: A structured electronic database search (MEDLINE, EMBASE, CONTROL; inception - December 2021) of the scientific literature was performed for studies reporting rates of AF recurrence following catheter ablation stratified by patients’ level of alcohol consumption. Alcohol use was dichotomized into categories which represented moderate-heavy alcohol use or those that represented abstention or rare alcohol use. Study specific odds rations (ORs) were meta-analyzed using a random effects model. Risk of bias was evaluated using the ROBINS-I tool. Results: A total of nine observational studies were identified, which included 5436 patients undergoing catheter ablation. There was substantial variation in the categories used to stratify alcohol consumption. Compared to patients consuming little to no alcohol, patients consuming moderate to high amounts of alcohol had a greater odds of AF recurrence (OR 1.45 [95% CI: 1.06-1.99, p = 0.02]; I 2 = 79%). This relationship remained significant after exclusion of studies with &lt; 100 participants (OR 1.40, 95% CI 1.03-1.90, p = 0.03) and when abstract-only publications were excluded (OR 1.84, 95% CI 1.21-2.80, p = 0.004). All included studies were found to be at serious risk of bias, mainly due to confounding. There was no evidence of publication bias. Conclusions: Increased alcohol consumption is associated with increased rates of AF recurrence following catheter ablation for AF. Reduction of alcohol consumption post ablation may reduce AF recurrence.
Abstract 11026: Proteomic Signatures of Ischemic and Non-Ischemic Heart Failure in a Community Cohort
Authors: Kayode O Kuku, Ho Young Park, Joe J Shearer, Jungnam Joo, Brittany Dulek, Suzette J Bielinski, Veronique L Roger
Journal: Circulation (2022)

Introduction: Coronary disease is the most common cause of heart failure (HF). HF is classified as ischemic (IHF) or non-ischemic (NIHF) based on this etiology. IHF and NIHF have distinct mechanisms not accounted for by ejection fraction (EF) and an improved understanding of the differences could drive the discovery of novel therapeutic targets. We therefore sought to identify proteomic signatures between IHF and NIHF. Methods: Proteomic profiling using the SomaScan®1.7K was performed using plasma samples from HF patients in a community cohort (Rochester Epidemiology Project, 2003-2012). IHF was defined by prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft, or obstructive disease in at least 1 vessel on coronary angiography. We compared the protein expression levels between IHF and NIHF using t-test and applied the Benjamini-Hochberg false-discovery rate (FDR) procedure for multiple comparisons. We explored pathway analysis for functional annotations using the biological process component of the Gene Ontology Resource (Panther 17v). Results: Among 1,388 patients, there were 518 IHF patients (age: 75±12years, 39.4% female, NYHA Class III/IV: 72.5%, EF:45±15%), and 870 NIHF patients (age: 75±14years, 53.6% female, NYHA Class III/IV: 66.9%, EF:49±17%). Among 7335 plasma proteins quantified, 63 unique proteins (FDR &lt; 0.05) were differentially expressed between IHF and NIHF. Thirty-seven proteins including Troponin-I and T, and Myoglobin showed increased expression in IHF compared to NIHF and 26 including IGFBP-3 showed decreased expression. Pathophysiologic pathways including angiogenesis, coagulation, and lipid metabolism were represented in IHF, while inflammation and remodeling signaling pathways were dominant in relation to NIHF. Conclusions: High-throughput proteomic techniques are able to delineate IHF versus NIHF patients based on distinct biomarkers and pathophysiologic processes.
Abstract 11874: Clinical Outcomes and Predictors of Long-Term Survival in Patients With and Without Extra-Cardiac Sarcoidosis Using Machine Learning: A Swedish Multicenter Study
Authors: Emanuele Bobbio, Per Eldhagen, Christian L Polte, Clara Hjalmarsson, Susanna Kullberg, Peder Sorensson, Niklas Bergh, Entela Bollano
Journal: Circulation (2022)

Introduction: Sarcoidosis is a systemic disease but cardiac involvement (CS) as first organ manifestation is not uncommon. Hypothesis: Patients with CS as the first manifestation of sarcoidosis has worse outcome compared to patients with known extra cardiac sarcoidosis (ECS) Methods: A retrospective cohort of 141 patients with CS enrolled at two Swedish university hospitals was studied. Presentation, treatment and outcomes of de novo CS and previous-known extra-CS group (ESC) were compared. Survival free time of primary composite outcome (ventricular tachycardia /ventricular fibrillation , heart transplantation , or death) was assessed. Using a data-driven approach with a machine learning (ML) algorithm, we studied the relative importance of several factors Results: 62 de novo CS patients and 79 with known ECS at time of cardiac manifestation. No difference in the demographics was observed between the groups. De novo CS patients showed more advanced NYHA class (p=0.02) as well as higher circulating levels of natriuretic peptides (p&lt;0.001), troponins (p&lt;0.001). Imaging findings were similar between the two groups. During a median (IQR) follow-up time was 28 [16-80] months, the composite end-point occurred in 37% of patients with CS as first clinical manifestation and in 20% of patients with ECS. Kaplan-Meier analysis showed that event-free survival was significantly worse in patients with de novo CS (p&lt;0.001) ( Fig. 1 ). The top four factors to predict event-free survival in order of importance were: tricuspid annular plane systolic excursion (TAPSE), Cardiac Index (CI), Right Ventricular (RV) ejection fraction, previous known ECS Conclusions: Patients presenting with CS as their first recognized organ manifestation of disease display worse outcomes compared to patients with previous-known ECS. Using machine learning, we show that the most important predictor of survival in CS is TAPSE, following by CI, RV ejection fraction and previous known ECS
Abstract 11822: Pivotal Trial of a Deep-Learning-Based Retinal Biomarker (Reti-CVD) in the Prediction of Cardiovascular Disease: Data From CMERC-HI
Authors: Tyler Hyungtaek Rim, Chan Joo Lee, Joseph Yi, Geunyoung Lee, Marco Yu, Yih-Chung Tham, Tien Y Wong, Ching-Yu Cheng, Dong Wook Kim, Sung Soo Kim, Sung Ha Park
Journal: Circulation (2022)

Introduction: The Korean Ministry of Food and Drug Safety (K-MFDS) has authorized over 110 artificial intelligence (AI)-software as medical devices (AI-SaMDs) for diagnostic purposes. Herein, we clinically validate the efficacy of a three-tier cardiovascular disease (CVD) risk stratification system developed using Reti-CVD, an AI-SaMD that utilizes retinal images to estimate CVD risk. The aim of this study is to evaluate the efficacy of RetiCVD in predicting future CVD risk based on retrospective analysis of a prior prospective cohort study. Methods: This clinical study was a single-center, retrospective, conformity-design, confirmatory analysis of prior prospective cohort study. For primary endpoint, retinal images were evaluated by Reti-CVD to validate its three-tier CVD risk stratification system. For secondary endpoints, cardiac CT-measured coronary artery calcium (CAC, 0, &gt;0-100, and &gt;100), carotid intima-media thickness (CIMT, &lt;90 th and ≥90 th percentile), and brachial-ankle pulse wave velocity (baPWV, &lt;1800 and ≥1800 cm/s) were also measured as independent variables for future CVD risk. The cumulative incidence of non-fatal and/or fatal CVD events was evaluated. Cox proportional hazards models were used to estimate the hazard ratios (HR) trends. Results: In this clinical cohort (n=1106), 33 (3.0%) participants had non-fatal or fatal CVD events over 5 years, and RetiCVD scores were significantly associated with increased CVD risk (HR trend=2.02, 95% CI, 1.26-3.24). In a multivariable Cox model incorporating RetiCVD scores, CAC, CIMT, baPWV, and other traditional risk factors, RetiCVD scores for the high-risk tier were significantly associated with increased CVD risk (low risk as a reference; HR=3.56 [1.34-9.51] in high risk), while other biomarkers showed trends toward association: CAC showed a HR of 2.45 [0.88-6.84] in CAC of &gt;100 compared to zero CAC (reference); CIMT showed a HR of 1.50 (0.64-3.51) in CIMT of ≥90 th percentile compared to &lt;90 th percentile; and baPWV showed a HR of 1.27 (0.53-3.03) in baPWV of ≥1800 compared to &lt;1800 cm/s. Conclusions: This is the first K-MFDS approved AI-software that can potentially stratify future risk as biomarkers, which can have major implications such as identifying high-risk individuals.
Abstract 10258: Rivaroxaban to Improve Clinical Outcomes in Outpatients With Covid-19: A Meta-Analysis of Two Randomized Clinical Trials
Authors: Judith A Hsia, Alex Spyropoulos, Gregory Piazza, Stephen Weng, Michael Dunne, Concetta Lipardi, Elliot S Barnathan, Marc P Bonaca
Journal: Circulation (2022)

Background: Thromboprophylaxis with rivaroxaban 10 mg once daily has been shown to reduce the risk of major thrombotic events in patients with COVID-19 both in-hospital and after discharge. The potential role of thromboprophylaxis with rivaroxaban in high-risk outpatients with COVID-19 was examined in 2 randomized, controlled trials; pooled analyses of these studies will enable evaluation of consistency of findings. Methods: PREVENT-HD (NCT04508023) and the Bill and Melinda Gates Medical Research Institute (Gates MRI) study (NCT04504032) are both virtually conducted, pragmatic trials which randomized patients with acute COVID-19 to rivaroxaban 10 mg daily or placebo (PREVENT-HD)/placebo equivalent (Gates MRI) on top of standard care (Figure). Both studies collected clinical outcomes including all-cause hospitalization, death, thrombotic and bleeding events. A patient-level meta-analysis was prespecified prior to PREVENT-HD database lock. Results: The 2 trials randomized a total of 1,781 patients. PREVENT-HD closeout is ongoing with anticipated unblinding in July 2022 and submission to AHA as an LBCT. Gates MRI study results have been reported; among the 497 randomized patients, clinical events were infrequent overall, with hospitalizations in 3 (1.4%) patients receiving rivaroxaban and 7 (3.2%) in the placebo group (RR 0.43, 95% CI 0.11, 1.65; p=0.21). A planned pooled analysis will occur after PREVENT-HD database lock enabling presentation at AHA 2022 if selected. Conclusions: A patient-level meta-analysis of 2 randomized, controlled trials of similar design evaluating rivaroxaban 10 mg daily for pre-hospital prevention of thrombotic complications, hospitalization, and death in outpatients with COVID-19 will be conducted. We hope to present the results at the AHA Scientific Sessions.
Abstract 11816: Association of Increased Adiposity and Presentation and Outcomes for Kawasaki Disease versus Multisystem Inflammatory Syndrome in Children Associated With Covid-19
Authors: Michael Khoury, Aishwarya Venkataraman, Michael A Portman, Marianna Fabi, Nagib Dahdah, Supriya Jain, Pei-Ni Jone, Geetha Raghuveer, Simon Lee, Deepa Prasad, Mona El Ganzoury, Angela T Yetman, Kevin G Friedman, Luis Martin Garrido, Kambiz Norozi, Anupam Sehgal, Ryan M Serrano, Shelby Kutty, Pedrom Farid, Brian W McCrindle
Journal: Circulation (2022)

Introduction: Obesity is a pro-inflammatory state and may influence presentation and outcomes of both Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Methods: From January 2020 to January 2022, n=2566 contemporaneous KD, MIS-C and acute COVID-19 pediatric patients from 39 sites in 8 countries were enrolled into the International KD Registry. The study population was confined to 1077 MIS-C patients meeting CDC criteria with confirmed or probable COVID-19 infection, and 657 KD patients meeting AHA guideline criteria without COVID-19 infection who had body mass index (BMI) recorded at presentation. BMI was converted to Z scores using WHO formulas for age and sex, and associated factors were sought using general linear regression modeling. Results: Mean zBMI was higher for MIS-C (+0.58) vs KD patients (-0.06; p&lt;0.001), and MIS-C patients were more likely to be overweight (BMI 85 th -&lt;95 th %ile; 18% vs 11%), obese (95 th -&lt;99 th %ile; 14% vs 6%) or morbidly obese ( &gt; 99 th %ile; 8% vs 2%; p&lt;0.001). MIS-C patients were significantly more likely to present with shock, and had higher peak troponin I and NTproBNP, with no association or interaction with adiposity. Higher adiposity was significantly associated with higher peak white cell count for MIS-C but not KD. Higher peak CRP for MIS-C and higher peak ESR for KD were not associated with adiposity. Higher peak creatinine was associated higher adiposity, more so for MIS-C. Both higher adiposity and MIS-C were significantly associated with lower LV ejection fraction, although there was no significant interaction (Figure A). Higher maximum coronary artery Z score was associated with KD but not with adiposity, with no significant interaction (Figure B). Conclusions: MIS-C patients have higher levels of adiposity than KD patients. Higher adiposity is associated with greater renal dysfunction in the setting of MIS-C, and greater cardiac dysfunction in both MIS-C and KD.
Abstract 12668: Coronary CTA Finding of Libman Sacks Endocarditis Presenting as Chest Pain
Authors: Omofolarin Babayale, Oluwaseun E Fashanu, David Corteville, bipul baibhav
Journal: Circulation (2022)

Case Presentation: A 65-year-old female with a history of hypertension, hyperlipidemia, microscopic colitis, fibromyalgia, left hand dupuytren's contractures, Grave’s disease and seronegative rheumatoid arthritis presented to the outpatient office for evaluation of right sided stabbing and heavy chest pain. ECG showed sinus bradycardia without any ST segment changes. She had an Echo and exercise stress Echo prior to her office visit. Her echo showed normal left ventricular size and systolic function with no regional wall motion abnormality and thickened aortic valve with mild aortic stenosis (peak transvalvular gradient 9.9 mmHg and mean 5.9 mmHg). Her stress echo was negative for ischemia although submaximal (exercised for 6.05 minutes, achieving only 75% MPHR, and double product of 18720). It was then decided to pursue a coronary CTA given the suboptimal nature of her stress testing and intermediate pretest probability of coronary artery disease. This revealed mild-to-moderate non-obstructive CAD and thickening of her left coronary cusp. The thickening was concerning for Libman-Sacks endocarditis vs native aortic valve thrombosis (see figure). Her Antinuclear antibody (ANA) titers was 1280. She was started on therapeutic anticoagulation with a plan for repeat imaging in six months. Discussion: Coronary cusp thickening represents a variety of differentials and has comparable structural and clinical qualities. Atypical chest pain in our patient led to the incidental finding of left coronary cusp thickening. In the presence of elevated ANA and her autoimmune disorder, Libman-Sacks endocarditis vs native aortic valve thrombosis was suspected hence the initiation of anticoagulation. Both have a propensity for fatal outcomes including, but not limited to myocardial infarction, embolic events, cardiogenic shock, or death. Follow-up imaging with a resolution of thrombus would confirm the diagnosis of native aortic valve thrombus.
Abstract 11140: The Role of Cardiac Extracellular Vesicles in Tumor Growth
Authors: Tal Caller, Olga Shaihov–Teper, Yeshai Schary, Daria Lendengolts, Itai Rotem, Racheli Peled, Ruty Shai, Efrat Glick-Saar, Dan Dominissini, Alex Boomgarden, Crislyn D'Souza-Schorey, Nili Naftali Shani, Jonathan Leor
Journal: Circulation (2022)

Background and aim: Heart disease may promote tumor growth (reverse cardio-oncology). However, the cellular and molecular mechanisms that link heart disease to cancer remain elusive, and specific therapies are limited. We hypothesized that the diseased heart secret extracellular vesicles (cEVs) that carry and disseminate pro-tumorigenic factors. Methods &amp; Results: We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling was confirmed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. Thus, we isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI. cMSCs after MI secreted more small EVs than cMSCs from sham-MI. Proteomic analysis revealed a distinctive profile of cEVs after MI ( Fig A ). In addition, cMSC-EVs after MI encapsulated more pro-tumorigenic cytokines: periostin, osteopontin, IL-6 and TNFα and microRNA: mir-221, mir-21, mir-24 and mir-214 with tumorigenic potential ( Fig B ). cMSC-EV uptake by breast and lung cancer cells was demonstrated in vitro. Next, a scratch assay showed that MI-cEVs facilitated cancer cell proliferation and migration two times faster than sham-MI cEVs ( Fig C , p=0.0002). Finally, lung or breast cancer cells were inoculated into the hind limb or mammary pad 10 days before or after MI. Serial ultrasound examinations monitored tumor growth. While MI stimulated tumor growth, EV inhibition by GW4869 markedly attenuated this effect ( Fig D ). Conclusions: We show, for the first time, that mesenchymal stromal cells from the infarcted heart secret extracellular vesicles that carry pro-tumorigenic factors, target cancer cells, and facilitate tumor growth. Thus, cardiac extracellular vesicles could be considered as therapeutic target in patients with concomitant heart disease and cancer.
Abstract 12406: Sglt2i Dapagliflozin Associated to Berberine Reduces Cardiac Cell Apoptosis and Necrosis During Exposure to Her-2 Blocking Agents Through Induction of Pampk and Reduction of Inflammasome, Il-6, Methylglyoxal and Leukotrienes-B4 Levels
Authors: Nicola Maurea, Simona Buccolo, Irma Bisceglia, Maria Laura Canale, Sara Scala, Andrea Paccone, Marino Scherillo, Vincenzo Quagliariello
Journal: Circulation (2022)

Introduction: Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In DAPA-HF trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Hypothesis: To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER-2 blocking agent-induced cardiotoxicity Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes-B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL-6 was performed Results: Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p&lt;0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL-6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group). Conclusions: Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.